Dibromocarbene compounds

Direct attachment of a functional group to the carbon atoms of the cyclopropane ring is fairly difficult. gem-Dibromocyclopropanes are readily available through the addition of dibromocarbene to olefinic compounds. Their synthetic versatility is reviewed in a previous volume of this series [77]. Substitution of the bromide with the aid of nucleophilic organometallics to form a new carbon-carbon bond has been investigated [78]. 

Our approach to the synthesis of model compounds, suited for the generation of carbenes, which are bound to the bridgehead of a strained bicyclic system, used the facile synthesis of [n.l.ljpropellanes, which we developed some years ago. Starting from substituted allyl chlorides 35, dibromocarbene addi-... 

Because of the yield of only 16% in the synthesis of 239, the overall yields of cycloadducts with reference to indene according to Scheme 6.54 are rather low, however. A substantial improvement was achieved by the development of a one-pot procedure, which starts from indene and takes advantage of its dibromocarbene adduct (254) (Scheme 6.55). This was prepared at -60 °C with tetrabromomethane and MeLi as source for the carbene and remained unchanged in solution up to temperatures around 0 °C [92]. If an activated alkene and MeLi were added sequentially to such a solution at -30 C, cydoadducts of 221 were isolated in a number of cases in relatively good yields. In Scheme 6.55, this procedure is illustrated by the example of 1,3-cyclopentadiene, which furnished the [4 + 2]-cydoadducts 255 and 256, both as a mixture with endo exo= 2 1, in the ratio of 8 1 in 23% yield with reference to indene [67]. Analogously, the products from 221 and styrene, 1,3-butadiene [92] and 2,3-dimethylbutadiene [66], namely the compounds 240, 241, 246-249 and 250-253, were obtained in yields of 40, 24 and 25%, respectively, by means of the one-pot procedure from indene. 

Methylisoquinol-l-one behaves as an enamine with dichlorocarbene to produce the dichlorocyclopropane derivative (83%). The corresponding reaction with dibromocarbene produces a thermally labile compound, which is assumed to have an analogous structure. Rearrangement of the dichloro compound under basic conditions leads to the isoindole derivative (96%), whereas controlled thermolysis... 

In practice, the synthesis of compound 13 was carried out according to Scheme 4.15, in which the "dibromocarbene" was substituted for "methylene" in order to exert better control of the reaction and thus giving the monoadduct as the predominant reaction product [31]. Although this meant an extra step in the synthetic sequence, the great selectivity and the excellent yields obtained compensated this "deviation" from the original retrosynthetic scheme. 

Introduction of the allene structure into cycloalkanes such as in 1,2-cyclononadiene (727) provides another approach to chiral cycloalkenes of sufficient enantiomeric stability. Although 127 has to be classified as an axial chiral compound like other C2-allenes it is included in this survey because of its obvious relation to ( )-cyclooctene as also can be seen from chemical correlations vide infra). Racemic 127 was resolved either through diastereomeric platinum complexes 143) or by ring enlargement via the dibromocarbene adduct 128 of optically active (J3)-cyclooctene (see 4.2) with methyllithium 143) — a method already used for the preparation of racemic 127. The first method afforded a product of 44 % enantiomeric purity whereas 127 obtained from ( )-cyclooctene had a rotation [a]D of 170-175°. The chirality of 127 was established by correlation with (+)(S)-( )-cyclooctene which in a stereoselective reaction with dibromocarbene afforded (—)-dibromo-trans-bicyclo[6.1 0]nonane 128) 144). Its absolute stereochemistry was determined by the Thyvoet-method as (1R, 87 ) and served as a key intermediate for the correlation with 727 ring expansion induced... 

Cyclic allenes have been obtained in high yields, as illustrated by the synthesis of 1,2-cyclononadiene from the dibromocarbene adduct of the readily available cyclooctene (equation 51).138 The smallest stable cyclic allene known to date is (14) it was prepared from the dibromocyclopropane (13) in high yield.139 A small amount of the tricyclic compound (15) was also obtained (equation 52). The cyclic allene (14) did not undergo dimerization even on prolonged standing at ambient temperatures. In contrast, the unsubstituted analog was detected only at -60 °C by H NMR. It should also be noted that cyclohexa-1,2-diene was generated by the reaction of methyllithium on dibromobicyclo[3.1.0]hexane and trapped as the Diels-Alder adduct.160... 

The most common synthetic reaction of carbenes is their addition to double bonds to form cyclopropane rings. For example, dibromocarbene adds to cyclohexene to give an interesting bicyclic compound. 

Carbenes are also formed by reactions of halogenated compounds with bases. If a carbon atom has bonds to at least one hydrogen and to enough halogen atoms to make the hydrogen slightly acidic, it may be possible to form a carbene. For example, bro-moform (CHBr3) reacts with a 50% aqueous solution of potassium hydroxide to form dibromocarbene. 

Again, much efficiency was gained by switching from alkoxy to siloxycyclopropanes . Dibromocarbene addition to silyl enol ethers generates cyclopropanes which open to a-bromo a,j5-unsaturated carbonyl compounds on thermolysis or treatment with acid in methanol (equation 137) . It has been shown that this homologation process also works for siloxycyclopropanes obtained by addition of other carbenoids (equation and that it is useful for terpene preparation . ... 

Unsaturated compounds (especially cyclic ones), which possess allylic C-H bond(s), are prone to insertion of dibromocarbene, in addition to cycloaddition to the double bond. Due to the similar physical properties of these products, their separation is troublesome, e.g. formation of 4 and 5. ... 

In the case of compounds with a fixed c -l,3-diene system, 1,4-addition may compete with 1,2-addition of dibromocarbene, e.g. formation of 6 and 1. ... 

Allenes react with dibromocarbene in a similar manner to the way they react with dichloro-carbene 1,1-di- and trisubstituted compounds afford adducts at the more highly substituted double bond, e.g. formation of 3. °... 

Dibromocarbene generated by solid-liquid phase-transfer catalysis undergoes addition to 1-aryl-2-aryltelluroethenes to give 3-aryi-2-aryltelluro-l,l-dibromocyclopropanes 1, with retention of configuration.The products were isolated by column chromatography and appeared to be fairly stable compounds. 

The first synthesis of this class of monocyclic diallenes has been reported by Sondheimer and co-workers (59, 60). They treated the dibromocarbene adduct 35 with (-)-sparteine-CH3Li complex at -10°C to obtain 36 (D2 symmetry), m.p. 113-116°C, [a] D +24.4°, together with the optically inactive meso 37 (C2h symmetry) m.p. 86-87.5°C. X-ray crystallographic data (61) have become available which show that the only isolable isomer of 1,2,6,7-cyclodecatetraene, m.p. 36°C (62), a lower homolog of 37 (X=H2), has a center of symmetry, indicating that this is a meso compound with C2h symmetry. 

Reactions of methyl (/ )-2-toY-butvl-2,3-dihydrooxazole-3-carboxylates with dichlorocarbene or dibromocarbene provide the expected cycloadducts as single diastereomers16. These compounds can serve as enantiomerically pure building blocks for further synthetic transformations. 

Di, tri-, and tetrahalocyclopropenes undergo cycloaddition with diazoalkanes to give unstable pyrazolines, which readily rearrange to pyridazines with loss of hydrogen halide. Tetrachlorocyclopropene is commercially available but many of the bromo compounds are easily prepared in two steps from vinyl bromides by addition of dibromocarbene, followed by reaction with methyllithium, the last step being carried out in situ for the cycloaddition step. ... 

The reaction of Ru(CO)2(PPhj)2(CF3)(HgCF3) with Br2 in CH2Q2 yields RuBr(CO)2(PPh3)2(CF3) (82%). The attempted preparation of the dibro-mocarbene complex by the reaction of the bromo Ru(II) compound with BBrj, however, resulted in the separation of the bicyclic RuBr2(CO)[=CCgH4PPh2)2] instead. The last product can be viewed as arising from the intramolecular elimination of 2 mol of HBr from the expected dibromocarbene complex (56). 

---